New Study Indicates Autism Begins During Pregnancy

A new study from the University of California, San Diego School of Medicine and the Allen Institute for Brain Science provides evidence that the development of autism begins during pregnancy.

For this study, 25 genes in the post-mortem brain tissue of children both with autism and without were analyzed. Researchers included Eric Courchesne, PhD, professor of neurosciences and director of the Autism Center of Excellence at UC San Diego, Ed Lein, PhD, of the Allen Institute for Brain Science in Seattle, and Rich Stoner, PhD, of the UC San Diego Autism Center of Excellence. The genes studied included those that function as biomarkers for brain cell types located in different layers of the cortex, genes that are implicated in autism, as well as several control genes.

“Building a baby’s brain during pregnancy involves creating a cortex that contains six layers,” Courchesne said. “We discovered focal patches of disrupted development of these cortical layers in the majority of children with autism.”

Stoner developed the first three-dimensional model that displayed visualization of brain locations where patches of the cortex did not develop in the normal cell-layering pattern.

“The most surprising finding was the similar early developmental pathology across nearly all of the autistic brains, especially given the diversity of symptoms in patients with autism, as well as the extremely complex genetics behind the disorder,” explained Lein.

Early in the development of the brain, specific types of brain cells are developed in each cortical layer. The pattern of brain connectivity in every layer is unique and performs important roles for processing information. During the development of brain cells into specific types and layers with specialized connections, a distinct genetic signature or “marker” is acquired and allows for later observation.

In this study, researchers discovered that key genetic markers were missing in the brain cells of multiple layers for children with autism. “This defect,” Courchesne said, “indicates that the crucial early developmental step of creating six distinct layers with specific types of brain cells – something that begins in prenatal life – had been disrupted.”

An equally important observation was how the early developmental defects were present in focal patches of cortex. This suggests that the defect is not uniform in the cortex. The frontal cortex and temporal cortex were regions that displayed the most focal patches of absent gene markers. This provides a possible explanation for why different functional systems are affected across individuals with autism.

The frontal cortex is an area associated with higher-order brain functions such as complex communication and the comprehension of social cues. Language is associated with the temporal cortex. The frontal and temporal cortical layer disruptions discovered in this study may underlie the symptoms most commonly displayed in the autism spectrum. Interestingly, the visual cortex, which is an area of the brain associated with perception that is usually spared in autism, had no abnormal displays.

“The fact that we were able to find these patches is remarkable, given that the cortex is roughly the size of the surface of a basketball, and we only examined pieces of tissue the size of a pencil eraser,” said Lein. “This suggests that these abnormalities are quite pervasive across the surface of the cortex.”

Developed by a consortium of partners, the data collected for the Allen Brain Atlas, as well as the BrainSpan Atlas of the Developing Human Brain was funded by the National Institute of Mental Health. This information allowed researchers to identify the specific genes in the developing human brain that were used as biomarkers among the cell types of different layers.

Since typical study of autism relies on the study of adult brains and extrapolating backwards, researching the origins of autism is uniquely challenging. “In this case,” Lein noted, “we were able to study autistic and control cases at a young age, giving us a unique insight into how autism presents in the developing brain.”

“The finding that these defects occur in patches rather than across the entirety of cortex gives hope as well as insight about the nature of autism,” added Courchesne.

The presence of patchy defects instead of a uniform cortical pathology may provide an explanation for why many toddlers with autism exhibit clinical improvement from early treatment over time. This study provides evidence supporting the idea that children with autism can sometimes rewire connections in the brain to help circumvent early focal defects. This study provides hope that the understanding of these patches could help to explore new ways that the improvement occurs.